Dagmar Ísleifsdóttir, Maonian Xu, Elvar Örn Viktorsson and Elín Soffía Ólafsdóttir
Introduction:
Usnic acid (UA), a secondary metabolite from lichens, has garnered significant attention due to its wide array of biological activities and promising therapeutic applications. Notably, UA exhibits potent antimicrobial, anti-inflammatory, and antiproliferative properties, among others. In recent years, there has been growing interest in the synthesis of UA analogs aimed at enhancing its biological activity. However, it is noteworthy that the majority of reported analogs are derived from the (+)-UA enantiomer, with limited attention given to (-)-UA. Enantiomers, despite sharing identical chemical properties, often demonstrate divergent bioactivities. While evidence suggests that (+)-UA possesses enhanced antimicrobial properties, (-)-UA is frequently associated with heightened cytotoxicity. However, studies comparing the activity of the enantiomers under the same research conditions are lacking.
Methodology:
Analog series were synthesized from both the (+)-UA and (-)-UA enantiomers aimed to provide novel compounds with improved bioactivity and physicochemical properties. A key focus of our synthesis strategy involved the creation of an isoxazole derivative, which prior research has shown to have increased anti-proliferative activity. Subsequently, the synthesized isoxazole derivative underwent further modification processes, including carbamoylations and alkylations to explore potential enhancements in bioactivities.
Results:
Methods have been developed to functionalize UA with different substituents, resulting in the successful synthesis of UA isoxazole and UA carbamates.
Conclusions:
The successful synthesis of UA analogs, including UA isoxazole and UA carbamates, demonstrates the feasibility of modifying UA to explore its bioactivity further. Further experimentation and bioactivity assays will elucidate the specific effects of these modifications on antimicrobial, and antiproliferative activities.
